Mutation of Ha-Ras C Terminus Changes Effector Pathway Utilization
dc.contributor.author | Booden, Michelle | |
dc.contributor.author | Sakaguchi, Donald | |
dc.contributor.author | Buss, Janice | |
dc.contributor.author | Sakaguchi, Donald | |
dc.contributor.department | Zoology and Genetics | |
dc.contributor.department | Biochemistry, Biophysics and Molecular Biology | |
dc.date | 2018-02-18T12:09:05.000 | |
dc.date.accessioned | 2020-07-07T05:16:57Z | |
dc.date.available | 2020-07-07T05:16:57Z | |
dc.date.copyright | Sat Jan 01 00:00:00 UTC 2000 | |
dc.date.issued | 2000-01-01 | |
dc.description.abstract | <p>In PC12 cells, Ha-Ras modulates multiple effector proteins that induce neuronal differentiation. To regulate these pathways Ha-Ras must be located at the plasma membrane, a process normally requiring attachment of farnesyl and palmitate lipids to the C terminus. Ext61L, a constitutively activated and palmitoylated Ha-Ras that lacks a farnesyl group, induced neurites with more actin cytoskeletal changes and lamellipodia than were induced by farnesylated Ha-Ras61L. Ext61L-triggered neurite outgrowth was prevented easily by co-expressing inhibitory Rho, Cdc42, or p21-activated kinase but required increased amounts of inhibitory Rac. Compared with Ha-Ras61L, Ext61L caused 2-fold greater Rac GTP binding and phosphatidylinositol 3-kinase activity in membranes, a hyperactivation that explained the numerous lamellipodia and ineffectiveness of Rac(N17). In contrast, Ext61L activated B-Raf kinase and ERK phosphorylation more poorly than Ha-Ras61L. Thus, accentuated differentiation by Ext61L apparently results from heightened activation of one Ras effector (phosphatidylinositol 3-kinase) and suboptimal activation of another (B-Raf). This surprising unbalanced effector activation, without changes in the designated Ras effector domain, indicates the Ext61L C-terminal alternations are a new way to influence Ha-Ras-effector utilization and suggest a broader role of the lipidated C terminus in Ha-Ras biological functions.</p> | |
dc.description.comments | <p>This research was originally published in The Journal of Biological Chemistry. Michelle A. Booden, Donald S. Sakaguchi, and Janice E. Buss. Mutation of Ha-Ras C Terminus Changes Effector Pathway Utilization. <em><a href="http://dx.doi.org/10.1074/jbc.M001368200" target="_blank">The Journal of Biological Chemistry</a>. </em>2000, 275: 23559-23568. © the American Society for Biochemistry and Molecular Biology.</p> | |
dc.format.mimetype | application/pdf | |
dc.identifier | archive/lib.dr.iastate.edu/zool_pubs/42/ | |
dc.identifier.articleid | 1043 | |
dc.identifier.contextkey | 10206978 | |
dc.identifier.s3bucket | isulib-bepress-aws-west | |
dc.identifier.submissionpath | zool_pubs/42 | |
dc.identifier.uri | https://dr.lib.iastate.edu/handle/20.500.12876/92653 | |
dc.language.iso | en | |
dc.source.bitstream | archive/lib.dr.iastate.edu/zool_pubs/42/2000_Sakaguchi_MutationTreminus.pdf|||Sat Jan 15 00:12:33 UTC 2022 | |
dc.source.uri | 10.1074/jbc.M001368200 | |
dc.subject.disciplines | Biochemistry | |
dc.subject.disciplines | Cell and Developmental Biology | |
dc.subject.disciplines | Molecular Biology | |
dc.title | Mutation of Ha-Ras C Terminus Changes Effector Pathway Utilization | |
dc.type | article | |
dc.type.genre | article | |
dspace.entity.type | Publication | |
relation.isAuthorOfPublication | 917b7591-023b-4249-b9eb-ba479084bead | |
relation.isOrgUnitOfPublication | 4a2929da-5374-4338-b62f-f5fd9e156ef9 | |
relation.isOrgUnitOfPublication | faf0a6cb-16ca-421c-8f48-9fbbd7bc3747 |
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